Advanced platinum strategies for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited treatment options. Platinum chemotherapy is incorporated into several therapeutic strategies, but its clinical benefit is constrained by resistance, toxicity, and suboptimal patient stratification. Platinum-induced DNA crosslinking remains the principal mechanism underlying antitumor activity. Recent studies indicate that Pt(IV) prodrugs, multifunctional agents, subcellularly targeted complexes, and tumor-responsive delivery systems can extend platinum pharmacology beyond conventional cytotoxicity. In parallel, studies have revealed emerging vulnerabilities, including homologous recombination deficiency, immunogenic cell death, ferroptosis, and DNA damage response dependencies, that provide new opportunities to enhance efficacy and overcome resistance. Advanced translational models and biomarker-guided stratification may help translate these opportunities into more precise therapeutic strategies. In this article, we review these developments and discuss their implications for advanced platinum therapies in TNBC.